Bioactive substance in a barbed suture

ABSTRACT

Barbed surgical sutures are prepared with a bioactive agent thereon. In embodiments, the bioactive agent may be an antimicrobial or clotting agent deposited within the angle formed by the barb and the suture body. Placement of the bioactive agent in the angle between the barb and suture body enhances the delivery of the bioactive agent to wound tissue at the point of contact.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of and priority to U.S.Provisional Application Ser. No. 60/842,763, filed on Sep. 6, 2006, theentire disclosure of which is incorporated herein by reference.

TECHNICAL FIELD BACKGROUND OF RELATED ART

Barbed sutures, which are generally made of the same materials asconventional sutures, offer several advantages for closing woundscompared with conventional sutures. A barbed suture includes anelongated body that has one or more spaced barbs, which project from thesurface of the suture body along the body length. The barbs are arrangedto allow passage of the barbed suture in one direction through tissuebut resist movement of the barbed suture in the opposite direction.Thus, one advantage of barbed sutures has been the provision of anon-slip attribute.

Barbed sutures are known for use in cosmetic, laparoscopic andendoscopic procedures. Using barbed sutures enables the placement oftension in tissue with less slippage of the suture in the wound. Thenumber of suture barbs may be influenced by the size of the wound andthe strength required to hold the wound closed. Like a conventionalsuture, a barbed suture may be inserted into tissue using a surgicalneedle.

Bioactive agents such as antimicrobial agents have been associated withsurgical devices such as to prevent microbial infections during thewound healing process. It is also known to coat surgical sutures withantimicrobial compounds to prevent and treat microbial infections.

While antimicrobial agents have been used for surgical sutures and wounddressings to prevent infections, a continuing need exists for improvedbarbed sutures that can remain in vivo for extended periods of time withenhanced antimicrobial efficacy. There is also a need for easy andinexpensive methods of improving the antimicrobial characteristics ofbarbed sutures for extended periods of time thus permitting the use oflower amounts of antimicrobial agents to achieve the desiredantimicrobial effect in vivo. There is also a need for delivery of otherbioactive agents to wound sites to promote healing and the like.

SUMMARY

A surgical suture is provided having an elongated body comprising atleast one filament having a proximal end and a distal end. The sutureincludes barbs projecting from the elongated body towards at least oneend thereby forming an included angle of less than about 90 degreesbetween the barbs and the suture body. In embodiments, a bioactive agentmay be deposited within the barb angles, that is, the angle formedbetween the barb and suture surface.

In yet a further embodiment, a method for repairing tissue with thesutures of the present disclosure is also provided.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present disclosure will be described hereinbelow with reference to the figures wherein:

FIG. 1 is a perspective view of a barbed suture in accordance with thepresent disclosure attached to a needle; and

FIG. 2 is a perspective view of a bi-directional barbed suture attachedto a needle on each end;

FIGS. 3A-3C are plan views of a tubular insertion device utilized with abarbed suture in accordance with the present disclosure; and

FIGS. 4A-4B are plan views of a sheath utilized with a barbed suture.

DETAILED DESCRIPTION

Described herein are barbed surgical sutures. Sutures in accordance withthe present disclosure may be of monofilament or multifilamentconstruction. The suture may have both a proximal and distal end, withbarbs projecting from the elongated body towards at least one endthereby forming an included angle of less than about 90 degrees betweenthe barbs and the suture body. In embodiments, a bioactive agent may bedeposited within the barb angles, that is, the angle formed between thebarb and suture surface. Placement of a bioactive agent in the angleformed between the barbs and suture surface places the bioactive agentat precisely defined locations within a tissue wound closure, whichthereby provides a unique controlled and sustained release dosage form.

Barbed sutures in accordance with the present disclosure may be formedof degradable materials, non-degradable materials, and combinationsthereof. Suitable degradable materials which may be utilized to form themedical device include natural collagenous materials or synthetic resinsincluding those derived from alkylene carbonates such as trimethylenecarbonate, tetramethylene carbonate, and the like, caprolactone,valerolactone, dioxanone, polyanhydrides, polyesters, polyacrylates,polymethylmethacrylates, polyurethanes, glycolic acid, lactic acid,glycolide, lactide, polyhydroxy butyrates (PHB), polyorthoester,polyhydroxy alkanoates, homopolymers thereof, copolymers thereof, andcombinations thereof. In some embodiments, glycolide and lactide basedpolyesters, especially copolymers of glycolide and lactide may beutilized to form a suture of the present disclosure.

Suitable non-degradable materials which may be utilized to form thesutures of the present disclosure include polyolefins, such aspolyethylene, polypropylene, copolymers of polyethylene andpolypropylene, and blends of polyethylene and polypropylene; ultra highmolecular weight polyethylene, polyamides (also known as nylon);polyesters such as polyethylene terephthalate; polytetrafluoroethylene;polyether-esters such as polybutester; polytetramethylene ether glycol;1,4-butanediol; polyurethanes; and combinations thereof. In otherembodiments, non-degradable materials may include silk, cat gut, cotton,linen, carbon fibers, and the like. In some useful embodiments,polypropylene can be utilized to form the suture. The polypropylene canbe isotactic polypropylene or a mixture of isotactic and syndiotactic oratactic polypropylene.

Filaments used for forming sutures of the present disclosure may beformed using any technique within the purview of those skilled in theart, such as, for example, extrusion, molding and/or solvent casting.

In embodiments, the suture of the present disclosure may include a yarnmade of more than one filament, which may contain multiple filaments ofthe same or different materials. Where the sutures are made of multiplefilaments, the suture can be made using any known technique such as, forexample, braiding, weaving or knitting. The filaments may also becombined to produce a non-woven suture. The filaments themselves may bedrawn, oriented, crinkled, twisted, commingled or air entangled to formyarns as part of the suture forming process. In one embodiment amultifilament suture of the present disclosure can be produced bybraiding. The braiding can be done by any method within the purview ofthose skilled in the art.

Once the suture is constructed, it can be sterilized by any means withinthe purview of those skilled in the art.

Sutures in accordance with the present disclosure may be coated orimpregnated with one or more medico-surgically useful substances, e.g.,bioactive agents which accelerate or beneficially modify the healingprocess when the suture is applied to a wound or surgical site. Suitablebioactive agents include, for example, biocidal agents, antimicrobialagents, medicants, growth factors, anti-clotting agents, clottingagents, analgesics, anesthetics, anti-inflammatory agents, wound repairagents and the like, chemotherapeutics, biologics, protein therapeutics,antibodies, DNA, RNA, peptides, polysaccharides, lectins, lipids,anti-angiogenic drugs, polymeric drugs, and combinations thereof.

Bioactive agents include substances which are beneficial to the animaland tend to promote the healing process. For example, a suture can beprovided with a bioactive agent that may be deposited at the suturedsite. The bioactive agent can be chosen for its antimicrobialproperties, capability for promoting wound repair and/or tissue growth,or for specific indications such as thrombosis. In embodiments,combinations of such agents may be applied to a suture of the presentdisclosure.

The term “antimicrobial agent” as used herein includes an agent whichhelps the body destroy or resist pathogenic (disease-causing)microorganisms. An antimicrobial agent includes antibiotics,antiseptics, disinfectants and combinations thereof. Antimicrobialagents which are slowly released into the tissue can be applied in thismanner to aid in combating clinical and sub-clinical infections in asurgical or trauma wound site. In embodiments, suitable antimicrobialagents may be soluble in one or more solvents.

In embodiments, the following anti-microbial agents may be used alone orin combination with other with other bioactive agents described herein:an anthracycline, doxorubicin, mitoxantrone, a fluoropyrimidine,5-fluorouracil (5-FU), a folic acid antagonist, methotrexate, apodophylotoxin, etoposide, camptothecin, a hydroxyurea, a platinumcomplex, cisplatin, doxycycline, metronidazole,trimethoprim-sulfamethoxazole, rifamycins like rifampin, a fourthgeneration penicillin (e.g., a ureidopenicillin a carboxypenicillin,meziocillin, piperacillin, carbenicillin, and ticarcillin, and ananalogue or derivative thereof), a first generation cephalosporin (e.g.,cephazolin sodium, cephalexin, cefazolin, cephapirin, and cephalothin),a carboxypenicillin (e.g., ticarcillin), a second generationcephalosporin (e.g., cefuroxime, cefotetan, and cefoxitin), a thirdgeneration cephalosporin (e.g., naxcel, cefdinir, cefoperazone,ceftazidime, ceftriaxone, and cefotaxime), polyvinyl pyrrolidone (PVP),a fourth generation cephalosporin (e.g., cefepime), a monobactam (e.g.,aztreonam), a carbapenem (e.g., imipenem, ertapenem and meropenem), anaminoglycoside (e.g., streptomycin, gentamicin, tobramycin, andamikacin), an MSL group member (e.g., a macrolide, a long actingmacrolide, a lincosamide, a streptogramin, Erythromycin, Azithromycin,Clindamycin, Syneroid, clarithromycin, and kanamycin sulfate),tetracyclines like minocycline, fusidic acid, trimethoprim,metronidazole; a quinolone (e.g., ciprofloxacin, ofloxacin,gatifloxacin, moxifloxacin, levofloxacin, and trovafloxacin), a DNAsynthesis inhibitor (e.g., metronidazole), a sulfonamide (e.g.sulfamethoxazole, trimethoprim, including cefixime, spectinomycin,tetracycline, nitrofurantoin, polymyxin B, and neomycin sulfate),beta-lactam inhibitors like sulbactam, chloramphenicol, glycopeptideslike vancomycin, mupirocin, polyenes like amphotericin B, azoles likefluconazole, and other known antimicrobial agent known in the art.

Examples of antiseptics and disinfectants which may be utilized as theantimicrobial agent include hexachlorophene; cationic biguanides likechlorhexidine and cyclohexidine; iodine and iodophores likepovidone-iodine; halo-substituted phenolic compounds like PCMX (i.e.,p-chloro-m-xylenol) and triclosan (i.e.,2,4,4′-trichloro-2′hydroxy-diphenylether); furan medical preparationslike nitrofurantoin and nitrofurazone; methenamine; aldehydes likeglutaraldehyde and formaldehyde; and alcohols. In some usefulembodiments, at least one of the antimicrobial agents may be anantiseptic such as triclosan.

To promote wound repair and/or tissue growth, one or more bioactiveagents known to achieve either or both of these objectives can also beapplied to the suture as wound repair agents or tissue growth agents.Such clotting or “fibrosis-inducing agents” are utilized for thepromotion of aneurysm or embolism when it is desired for treatment ofparticular vascular insults or diseases, or for example, blocking atumor from its primary blood supply. In embodiments, the barbed suturehaving a clotting agent deposited within the barb angles in accordancewith the present disclosure may contribute to platelet and bloodcomponent capture.

Examples of chemotherapeutics which may be utilized include one or moreof the following: doxorubicin (Dox), paclitaxel (PTX), or camptothecin(CPT), polyglutamate-PTX (CT-2103 or Xyotax),N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, anthracycline,letrozole, anastrozole, epidermal growth factor receptor inhibitors,tyrosine kinase inhibitors,modulators of apoptosis, anthracyclineantibiotics such as daunorubicin and doxorubicin, alkylating agents suchas cyclophosphamide and melphalan, antimetabolites such as methotrexateand 5-fluorouracil, poly(ethylene glycol) (PEG), poly(glutamic acid)(PGA), polysaccharides, polymer-drug conjugates thereof, copolymersthereof and combinations thereof.

The clotting agents include one or more of the following: a fibrosingagent that promotes cell regeneration, a fibrosing agent that promotesangiogenesis, a fibrosing agent that promotes fibroblast migration, afibrosing agent that promotes fibroblast proliferation, a fibrosingagent that promotes deposition of extracellular matrix, a fibrosingagent that promotes tissue remodeling, a fibrosing agent that is adiverticular wall irritant, silk (such as silkworm silk, spider silk,recombinant silk, raw silk, hydrolyzed silk, acid-treated silk, andacylated silk), talc, chitosan, polylysine, fibronectin, bleomycin or ananalogue or derivative thereof, connective tissue growth factor (CTGF),metallic beryllium or an oxide thereof, copper, saracin, silica,crystalline silicates, quartz dust, talcum powder, ethanol, a componentof extracellular matrix, collagen, fibrin, fibrinogen, poly(ethyleneterephthalate), poly(ethylene-co-vinylacetate), N-carboxybutylchitosan,an RGD protein, a polymer of vinyl chloride, cyanoacrylate, crosslinkedpoly(ethylene glycol)-methylated collagen, an inflammatory cytokine,TGFβ, PDGF, VEGF, TNFa, NGF, GM-CSF, IGF-a, IL-1, IL-8, IL-6, a growthhormone, a bone morphogenic protein, a cell proliferative agent,dexamethasone, isotretinoin, 17-β-estradiol, estradiol,diethylstibesterol, cyclosporine a, all-trans retinoic acid or ananalogue or derivative thereof, wool (including animal wool, wood wool,and mineral wool), cotton, bFGF, polyurethane, polytetrafluoroethylene,poly(alkylcyanoacrylate), activin, angiopoietin, insulin-like growthfactor (IGF), hepatocyte growth factor (HGF), a colony-stimulatingfactor (CSF), erythropoietin, an interferon, endothelin-1, angiotensinII, bromocriptine, methylsergide, fibrosin, fibrin, an adhesiveglycoprotein, proteoglycan, hyaluronan, secreted protein acidic and richin cysteine (SPaRC), a thrombospondin, tenacin, a cell adhesionmolecule, an inhibitor of matrix metalloproteinase, magainin, tissue orkidney plasminogen activator, a tissue inhibitor of matrixmetalloproteinase, methotrexate, carbon tetrachloride, thioacetamide,superoxide dismutase to scavenge tissue-damaging free radicals, tumornecrosis factor for cancer therapy, colony stimulating factor,interferon, interleukin-2 or other lymphokines to enhance the immunesystem, platelet rich plasma, thrombin, combinations thereof, and soforth.

A wide variety of anti-angiogenic factors may be readily utilized withinthe context of the present disclosure. Representative examples includeAnti-Invasive Factor; retinoic acid and derivatives thereof; paclitaxela highly derivatized diterpenoid; Suramin; Tissue Inhibitor ofMetalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2;Plasminogen Activator Inhibitor-1; Plasminogen Activator Inhibitor-2;various forms of the lighter “d group” transition metals such as, forexample, vanadium, molybdenum, tungsten, titanium, niobium, and tantalumspecies and complexes thereof; Platelet Factor 4; Protamine Sulphate(Clupeine); Sulphated Chitin Derivatives (prepared from queen crabshells); Sulphated Polysaccharide Peptidoglycan Complex (SP-PG) (thefunction of this compound may be enhanced by the presence of steroidssuch as estrogen, and tamoxifen citrate); Staurosporine; Modulators ofMatrix Metabolism, including for example, proline analogs{[(L-azetidine-2-carboxylic acid (LACA), cishydroxyproline,d,L-3,4-dehydroproline, Thiaproline, α,α-dipyridyl, β-aminopropionitrilefumarate; MDL 27032 (4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone;Methotrexate; Mitoxantrone; Heparin; Interferons; 2 Macroglobulin-serum;ChIMP-3; Chymostatin; β-Cyclodextrin Tetradecasulfate; Eponemycin;Camptothecin; Fumagillin Gold Sodium Thiomalate (“GST”); D-Penicillamine(“CDPT”); β-1-anticollagenase-serum; α2-antiplasmin; Bisantrene;Lobenzarit disodium (N-(2)-carboxyphenyl-4-chloroanthronilic aciddisodium or “CCA”; Thalidomide; Angostatic steroid; AGM-1470;carboxynaminolmidazole; metalloproteinase inhibitors such as BB94,analogues and derivatives thereof, and combinations thereof.

A wide variety of polymeric drugs may be readily utilized within thecontext of the present disclosure. Representative examples includesteroidal anti-inflammatory agents, non-steroidal anti-inflammatoryagents, and combinations thereof. Examples of the non-steroidalanti-inflammatory agent which may be used with the present disclosureare aspirin, indomethacin, ibuprofen, phenylbutazone, diflusinal, andcombinations thereof.

Examples of the steroidal anti-inflammatory agent which may be used areglucocorticoids such as cortisone and hydrocortisone, betamethasone,dexamethasone, fluprednisolone, prednisone, methylprednisolone,prednisolone, triamcinolone, paramethasone, and combinations thereof.

Although the above bioactive agents have been provided for the purposesof illustration, it should be understood that the present disclosure isnot so limited. In particular, although certain bioactive agents arespecifically referred to above, the present disclosure should beunderstood to include analogues, derivatives and conjugates of suchagents.

Sutures in accordance with this disclosure can also include, forexample, biologically acceptable plasticizers, antioxidants andcolorants, which can be impregnated into the filament(s) utilized toform a suture of the present disclosure or included in a coatingthereon.

As noted above, bioactive agents may be impregnated into the materialsutilized to form sutures of the present disclosure or deposited on thesurface thereof. Bioactive agents may be applied onto a barbed suture ofthe present disclosure utilizing any method within the purview of oneskilled in the art including, for example, dipping, spraying, vapordeposition, brushing, compounding and the like.

In embodiments the bioactive agent, such as an antimicrobial agent, maybe applied to a barbed suture of the present disclosure as part of abioactive agent solution. The bioactive agent solution can include anysolvent or combination of solvents suitable for the chosen bioactiveagent. To be suitable, the solvent should (1) be miscible with thebioactive agent, and (2) not appreciably affect the integrity of anymaterial used to form a medical device, such as the barbed suture. Insome useful embodiments, the solvent utilized is a polar solvent. Someexamples of suitable solvents include methylene chloride, chloroform,ethyl acetate, methyl acetate, N-methyl 2-pyrrolidone, 2-pyrrolidone,propylene glycol, tetrahydrofuran (THF), acetone, oleic acid, methylethyl ketone, water, and mixtures thereof. In one embodiment, methylenechloride may be used as a solvent.

The method of preparing the bioactive agent solution can be a relativelysimple procedure including mixing, blending, and the like. Any knowntechnique may be employed for applying the bioactive agent solution tothe medical device. Suitable techniques include dipping, spraying,wiping, brushing, and the like.

The bioactive agent solution generally contains from about 0.1% to about20% of the bioactive agent by weight, in embodiments from about 0.5% toabout 5% of the bioactive agent by weight. The exact amount of thebioactive agent will depend on a number of factors, such as theparticular agent used, the medical device being contacted and the choiceof solvent employed. In one embodiment, where the bioactive agent is anantimicrobial agent, the antimicrobial solution may contain from about0.1% to about 10% of the chosen antimicrobial agent, in embodiments fromabout 1% to about 5% of the antimicrobial agent.

The amount of the bioactive agent solution applied should be aneffective amount to provide the desired bioactive properties to thesuture. The exact amount will depend upon the configuration of thesuture and the formulation of the solution. Since the bioactive agentsolution contains a solvent, a curing step may be employed in usefulembodiments to remove the solvent, leaving the bioactive agent on thesuture. Suitable curing steps for removal of the solvent include, butare not limited to, evaporation and/or lyophilization. Upon removal ofthe solvent, the bioactive agent remains bound to the suture in theangle formed between the barb and suture body.

Regardless of the method of application, the amount of the bioactiveagent on the suture can be from about 0.01% by weight of the suture toabout 2% by weight of the suture, in embodiments from about 0.02% byweight of the suture to about 1% by weight of the suture, typically fromabout 0.05% by weight of the suture to about 0.5% by weight of thesuture.

Once applied, the bioactive agent will not be lost due to evaporation,sublimation, volatilization, etc. during the subsequent handling,processing and storage of the barbed suture. However, upon applicationof the barbed suture in vivo, that is, after use in suturing a wound,the attachment of the barbs to the tissue will release the bioactiveagent into the tissue.

In other embodiments, the bioactive agent may be included in a coatingapplied to the suture. Suitable coatings which may be utilized arewithin the purview of one skilled in the art and include, for example,biodegradable coatings such as those disclosed in U.S. PatentPublication No. 20040153125, the entire disclosure of which isincorporated by reference herein. Biodegradable polymers may beespecially suitable as they will release the bioactive agent in vivo asthe biodegradable polymer is resorbed by the body.

In embodiments, mixtures useful in forming the aforementioned coatingsinclude a bioactive agent such as an antimicrobial agent as apredominant component in an effective antimicrobial amount. A“predominant amount” refers to one or more components which are presentin an amount greater than about 50 weight percent. A “minor amount”refers to one or more components which are present in an amount up toabout 50 weight percent. The minor component may include copolymerscontaining biodegradable monomers such as caprolactone.

An “effective antimicrobial amount” of a given component is an amount atwhich the component hinders the growth of bacteria to diminish or avoidcontamination of the wound site.

In embodiments, the antimicrobial degradable coating composition forbiocompatible surgical implantable devices is inexpensive,biocompatible, and not subject to excessive diffusion. “Biocompatible”means that no serious systemic toxicity is caused by the presence of anobject in a living system. It is contemplated that biocompatible objectsmay cause some clinically acceptable amounts of toxicity includingirritation and/or other adverse reactions in certain individuals.

Any biodegradable polymer within the purview of those skilled in the artcan be employed in the present coatings. In embodiments, thebiodegradable polymer may contain epsilon-caprolactone as a componentthereof. Suitable caprolactone containing copolymers include copolymerswhich may be synthesized by well known conventional polymerizationtechniques. In some embodiments, suitable caprolactone containingcopolymers are “star” copolymers obtained by polymerizing a predominantamount of epsilon-caprolactone and a minor amount of anotherbiodegradable monomer polymerizable therewith in the presence of apolyhydric alcohol initiator.

In embodiments, the caprolactone containing copolymer may be obtained bypolymerizing a predominant amount of epsilon-caprolactone and a minoramount of at least one other copolymerizable monomer or mixture of suchmonomers in the presence of a polyhydric alcohol initiator. Thepolymerization of these monomers contemplates all of the various typesof monomer addition, i.e., simultaneous, sequential, simultaneousfollowed by sequential, sequential followed by simultaneous, etc.

In certain embodiments, the copolymer herein can contain from about 70to about 98, and preferably from about 80 to about 95, weight percentepsilon-caprolactone derived units, the balance of the copolymer beingderived from the other copolymerizable monomer(s).

Suitable monomers which can be copolymerized with epsilon-caprolactoneinclude alkylene carbonates such as trimethylene carbonate,tetramethylene carbonate, dimethyl trimethylene carbonate; dioxanones;dioxepanones; degradable cyclic amides; degradable cyclic ether-estersderived from crown ethers; hydroxyacids capable of esterification,including both alpha hydroxyacids (such as glycolic acid and lacticacid) and beta hydroxyacids (such as beta hydroxybutyric acid and gammahydroxyvaleric acid); polyalkyl ethers (such as polyethylene glycol andpolypropylene glycol and combinations thereof); polyvinyl pyrrolidone,hydroxyethylmethacrylate, phosphorylcholine, acrylic acid, methacrylicacid, vinyl monomers, vinyl alcohols, vinyl acetate, and combinationsthereof. In embodiments, a suitable monomer for use with the presentdisclosure is glycolide.

Suitable polyhydric alcohol initiators include glycerol,trimethylolpropane, 1,2,4-butanetriol, 1,2,6-hexanetriol,triethanolamine, triisopropanolamine, erythritol, threitol,pentaerythritol, ribitol, arabinitol, xylitol,N,N,N′,N′-tetrakis(2-hydroxyethyl)ethylenediamine,N,N,N′,N′-tetrakis(2-hydroxypropyl)ethylenediamine, dipentaerythritol,allitol, dulcitol, glucitol, altritol, iditol, sorbitol, mannitol,inositol, and the like; with mannitol being preferred.

The polyhydric alcohol initiator is generally employed in relativelysmall amounts, e.g., from about 0.01 to about 5, and preferably fromabout 0.1 to about 3, weight percent of the total monomer mixture.

The coating composition can contain from about 0.3 to about 10, andpreferably from about 0.5 to about 5, weight percent of the copolymer.Such a coating provides sutures with the combined desirable propertiesof improved handling characteristics and antimicrobial activity.

In addition to the antimicrobial agents described above, in someembodiments the coating may include one or more fatty acid componentssuch as fatty acids, fatty acid salts and salts of fatty acid esterswhich may impart antimicrobial characteristics to the suture.

Where the coating includes a fatty acid metal salt, the fatty acid metalsalt used as the antimicrobial agent may include metal stearates. In oneembodiment, the fatty acid salt used as the antimicrobial agent issilver stearate. In another embodiment, the fatty acid salt(s) used asthe antimicrobial agent may be combined with fatty acid esters such asstearoyl lactylates, particularly calcium stearoyl lactylate.

Suitable fatty acids which can be used in the present coatings includethe biocompatible monovalent and polyvalent metal salts of fatty acidshaving 6 or more carbon atoms. Examples of fatty acids useful forforming a metal salt of a fatty acid useful herein includes butyric,caproic, caprylic, capric, lauric, myristic, palmitic, palmitoleic,stearic, oleic, linoleic, linolenic, etc. Examples of monovalent metalsuseful for forming a metal salt of a fatty acid useful in the variousembodiments described herein include lithium, rubidium, cesium,francium, copper, silver and gold. Examples of polyvalent metals usefulfor forming a metal salt of a fatty acid useful in the variousembodiments described herein include aluminum, tin, lead, bismuth andthe polyvalent transition metals. Therefore, suitable metal salts offatty acids useful herein include fatty acid salts of lithium, rubidium,cesium, francium, copper, silver, gold, beryllium, magnesium, strontium,barium, radium, aluminum, tin, lead, bismuth, zinc, cadmium, mercury,etc.

The metal salt of a fatty acid is present in the coating composition inan effective antimicrobial amount as defined above. The metal salt of afatty acid can consist of a single chemical compound. However, the metalsalt of a fatty acid can also be a mixture of several metal salts offatty acids. The metal salt of a fatty acid may be present in an amountfrom about 30 percent to about 70 percent by weight of the coatingcomposition, in embodiments from about 45 percent to about 55 percent byweight of the coating composition.

The metal salt of a fatty acid may be relatively insoluble in coldwater. When desirable, a solvent may be used to improve the workingproperties, e.g., viscosity, miscibility, etc., of the metal salt of afatty acid. Suitable solvents include, for example, alcohols, e.g.,methanol, ethanol, propanol, chlorinated hydrocarbons (such as methylenechloride, chloroform, 1,2-dichloro-ethane), aliphatic hydrocarbons suchas hexane, heptene, ethyl acetate). When desirable, heat may be appliedto the solvent mixture of metal salts of fatty acids to improve theirsolubility. For example, temperatures ranging from about 30° C. to about60° C. are appropriate.

In certain embodiments, fatty acid esters may be combined with the metalsalt of a fatty acid in the coating composition. Such esters include,for example, calcium stearate, stearoyl lactylate esters, palmityllactylate esters, oleyl lactylate esters such as calcium, magnesium,aluminum, barium, or zinc stearoyl lactylate; calcium, magnesium,aluminum, barium, or zinc palmityl lactylate; calcium, magnesium,aluminum, barium, or zinc oleyl lactylate; with calcium stearate andcalcium stearoyl-2-lactylate (such as the calcium stearoyl-2-lactylatecommercially available under the tradename VERV from AmericanIngredients Co., Kansas City, Mo.) being preferred. When desirable, thefatty acid ester may be combined with a solvent. Suitable solventsinclude those listed above.

Where the bioactive agent is included as part of a coating, thebioactive agent and coating components may be added to separatesolvents, and the resulting solvent mixtures may then be combined toform a coating solution. In other embodiments, the bioactive agent andcoating components may be combined together and then mixed with solventto form a coating solution or any combination. The order of addition isnot critical and therefore may be determined through routineexperimentation depending upon the desired use.

The coating can be applied to a suture by any suitable process, e.g.,passing the suture through a solution of the coating mixture, past abrush or other coating solution applicator, or past one or more spraynozzles dispensing the suture coating solution. The coating solution cancontain from about 30 to about 70, in embodiments from about 45 to about55, weight percent solvent. In embodiments, a mixture of methylenechloride, hexane and ethanol may be used as a solvent. The suture wettedwith the coating solution may be optionally passed through or held in adrying oven for a time and at a temperature sufficient to vaporize anddrive off the solvent. If desired, the suture coating composition canoptionally contain additional bioactive agents or components describedabove, e.g., dyes, antibiotics, antiseptics, growth factors,anti-inflammatory agents, etc.

Barbs may be formed on the surface of the body of a suture utilizing anymethod within the purview of one skilled in the art. Such methodsinclude, but are not limited to, cutting, molding, and the like. In someembodiments, barbs may be formed by making with acute angular cutsdirectly into the suture body, with cut portions pushed outwardly andseparated from the body of the suture. The depth of the barbs thusformed in the suture body may depend on the diameter of the suturematerial and the depth of the cut. In some embodiments, a suitabledevice for cutting a plurality of axially spaced barbs on the exteriorof a suture filament may use a cutting bed, a cutting bed vise, acutting template, and a blade assembly to perform the cutting. Inoperation, the cutting device has the ability to produce a plurality ofaxially spaced barbs in the same or random configuration and atdifferent angles in relation to each other. Other suitable methods ofcutting the barbs include the use of a laser or manual methods. Thesuture could also be formed by injection molding, extrusion, stampingand the like. The suture can be packaged in any number of desiredpre-cut lengths and in pre-shaped curves.

In embodiments, all of the barbs may be aligned to allow the suture tomove through tissue in one direction and resist moving through tissue inthe opposite direction. For example, referring to FIG. 1, the barbs 12on a suture 10 may be formed into a single directional suture. Inembodiments suture 10 may be attached to needle 16. The barbs 12 areyieldable toward the body 14 of suture 10. The barbs 12 permit movementof suture 10 through tissue in the direction of movement of a needle end16 but are generally rigid in an opposite direction and prevent movementof suture 10 in a direction opposite the direction of movement of aneedle end 16.

Suture 10 may include a bioactive agent (not shown) disposed within theangle between the barb 12 and suture body 14.

Alternatively, a multifilament suture (not shown) may be utilized whichmay include filaments fabricated from biocompatible degradable polymers,biocompatible non-degradable polymers, or combinations thereof. Inembodiments, a multifilament suture may be provided which includes abiocompatible degradable polymer which includes a bioactive agentdisposed within the angle between the barb and suture body. In anotherembodiment, a multifilament suture may include individual filamentsfabricated from a combination of biocompatible degradable polymer orbiocompatible non-degradable polymer which includes a bioactive agentdisposed within the angle between the barb and suture body.

In other embodiments, the barbs may be aligned on a first portion of alength of a suture to allow movement of a first end of the suturethrough tissue in one direction, while barbs on a second portion of thelength of the suture may be aligned to allow movement of the second endof the suture in an opposite direction. For example, as depicted in FIG.2, a suture 110 may be bi-directional. Barbed suture 110 includes anelongated body 114 having two areas, body portion 114 a and body portion114 b, distal first and second needle ends 116 a and 116 b forpenetrating tissue, and a plurality of barbs 112 a and 112 b extendingfrom the periphery of the body 114. An antimicrobial agent may bedisposed within the angle formed between the barbs 112 a and 112 b andsuture body 114. Barbs 112 a on a first portion of the body 114 abetween the first end of suture 110 and a first axial location on thesuture body permit movement of suture 110 through the tissue in adirection of movement of first needle end 116 a and prevent movement ofsuture 110 relative to the tissue in a direction opposite the directionof movement of the first needle end 116 a. Barbs 112 b on second portionof body 114 b between a second needle end 116 b of a suture 114 and asecond axial location on the body which is less than the distance fromthe second needle end 116 b to the first axial location permit movementof a suture 114 through the tissue in a direction of movement of asecond needle end 116 b and prevent movement of a suture 114 relative tothe tissue in a direction opposite the direction of movement of thesecond needle end 116 b.

The barbs can be arranged in any suitable pattern, for example, in ahelical pattern. The number, configuration, spacing and surface area ofthe barbs can vary depending upon the tissue in which the suture isused, as well as the composition and geometry of the material utilizedto form the suture. Additionally, the proportions of the barbs mayremain relatively constant while the overall length of the barbs and thespacing of the barbs may be determined by the tissue being connected.For example, if the suture is to be used to connect the edges of a woundin skin or tendon, the barbs may be made relatively short and more rigidto facilitate entry into this rather firm tissue. Alternatively, if thesuture is intended for use in fatty tissue, which is relatively soft,the barbs may be made longer and spaced further apart to increase theability of the suture to grip the soft tissue.

The surface area of the barbs can also vary. For example, fuller-tippedbarbs can be made of varying sizes designed for specific surgicalapplications. For joining fat and relatively soft tissues, larger barbsmay be desired, whereas smaller barbs may be more suitable forcollagen-dense tissues. In some embodiments, a combination of large andsmall barbs within the same structure may be beneficial, for examplewhen a suture is used in tissue repair with differing layer structures.Use of the combination of large and small barbs with the same suturewherein barb sizes are customized for each tissue layer will ensuremaximum anchoring properties. In embodiments a single directional sutureas depicted in FIG. 1 may have both large and small barbs; in otherembodiments a bi-directional suture as depicted in FIG. 2 may have bothlarge and small barbs.

In embodiments, sutures of the present disclosure may be dyed in orderto increase the visibility of the suture in the surgical field. Any dyesuitable for incorporation in sutures can be used. Such dyes include,but are not limited to, carbon black, bone black, D&C Green No. 6, andD&C Violet No. 2. In embodiments, sutures in accordance with the presentdisclosure may be dyed by adding dye in an amount up to about a fewpercent, in other embodiments by adding dye in an amount of about 0.2%,in still further embodiments in an amount from about 0.06% to about0.08%.

In order to facilitate needle attachment to a suture of the presentdisclosure, conventional tipping agents can be applied to the braid. Twotipped ends of the suture may be desirable for attaching a needle toeach end of the suture to provide a so-called double armed suture. Theneedle attachment can be made by any conventional method such ascrimping, swaging, etc, as is known within the purview of those skilledin the art. Wounds may be sutured by passing the needled suture throughtissue to create wound closure. The coating, in addition to enhancingthe suture's handling characteristics, advantageously possessesantimicrobial properties to promote healing and prevent infection.

In some embodiments, the barb contribution to the architecture of thesuture or a wound closure device may contribute to platelet and bloodcomponent capture. Referring to FIGS. 3A, 3B, 3C, a tubular insertiondevice 22 may be utilized to introduce a barbed suture 10 in accordancewith the present disclosure into a blood vessel 20. Such a tubularinsertion device 22 may have a tubular body in which the barbed suture10 is disposed, as well as a distal end 24 and a proximal end 26. Inuse, the pointed end of a barbed suture 10 of the present disclosure maybe pushed with the distal end 24 of the tubular insertion device throughskin, tissue, vessels, and the like at an insertion point. The pointedend of barbed suture 10 and the distal end 24 of the tubular insertiondevice are pushed through the tissue until reaching an endpoint. Theproximal end 26 of the tubular insertion device 22 is then gripped andpulled to remove the insertion device 22, leaving the barbed suture 10in place.

For ease of movement of the tubular insertion device, the tubularinsertion device 22 may include a string, wire, or the like to pull andremove the insertion device 22 from the barbed suture as illustrated inFIG. 3B. In exemplary embodiments, the tubular insertion device 22 isdeployed from barbed suture 10, which allows for barbed suture 10 toexpand to full vessel thickness and anchor itself to the vessel 20. Asillustrated in FIG. 3C, the deployment of tubular insertion device 22and expansion of the barbed suture 10 allows for the capture ofcirculating platelets and blood components to instigate vascularblockage and/or clotting of vessel 20.

The barbed suture in FIGS. 3A-3C illustrates a flexible and bentconfiguration. However, it is envisioned that a variety of suture orfiber configurations may be employed. In other embodiments, fiberconfigurations may include twisting the barbed device within the sheath(not shown).

In an exemplary embodiment, where present, a tubular insertion devicesurrounding a barbed suture of the present disclosure protects thebioactive agent which is disposed within the barb angle formed by thebarb and the suture body. Thus, the tubular insertion device may aid inkeeping the barbed suture intact and the bioactive agent attached to thesurface of the suture during insertion, as well as during handling, andstorage of the suture. This minimizes the loss of bioactive agent to thepackaging of the medical device, the environment, etc. However, uponengaging the barbed suture and tubular insertion device in vivo, movingthe sheath relative to the suture to extract the sheath from the tissueexposes the bioactive agent to tissue and assists in the release ofbioactive agent from the interface of the barb and the suture body intothe wound closure. The barbed suture expands to full vessel thicknessand acts as an anchor to patient tissue.

In embodiments where a clotting agent is employed, the barbed suturealso captures circulating platelets and blood components and instigatesvascular blockage or clotting. If mechanical property requirements arenot too restrictive, a hydrogel or super-absorbent material may be usedto further concentrate blood components, or the barbed device may alsodrive and place the bhydrogel-like material to final placement.

Referring to FIGS. 4A-4B, a sheath 23 may be utilized to introducebarbed suture 10 in accordance with the present disclosure into bloodvessel 20. Such a sheath 23 may have a tubular body in which the barbedsuture 10 is disposed. In one embodiment, sheath 23 may be disposed atone end of barbed suture 10 and in other embodiments, sheath 23 may bedisposed on both ends of barbed suture 10 (not shown). In embodiments,sheath 23 may be formed of materials such as, but are not limited to,filament fibers, nylon fibers, polyester (PET), copolymer polyester(co-PET), polypropylene (PP), and polyethylene (PE). [please confirm]which are designed to swell in order to block vessel 20 and induceclotting as the barbs on the suture, fully engaged and expanded withinvessel 20, captures blood components and platelets to assist in theclotting. The barbed suture 10 may also include a bioactive agent withinthe included angle of the barb and the elongated body of the suture toenhance clotting of vessel 20.

Methods for repairing tissue with the sutures of the present disclosureare also provided. The sutures of the present disclosure may be utilizedin any cosmetic endoscopic or laparoscopic methods. In addition, suturesof the present disclosure may be utilized to attach one tissue toanother including, but not limited to, attaching tissue to a ligament.

In embodiments, sutures of the present disclosure may be held in placewithout the need for knots. In such cases, tissue located over a sutureof the present disclosure placed in vivo may be physically manipulatedor massaged into a desired position to enhance the holding of tissue inthe desired position. In embodiments, the physical manipulation oftissue located over a suture of the present disclosure may enhance therelease of any medicinal agent located on the suture, including anymedicinal agent found in the angle between a barb and the body of asuture of the present disclosure.

For example, sutures of the present disclosure may be utilized toprovide lift to tissue, which may be desirable in certain cosmeticapplications. In embodiments, a procedure for closing tissue utilizingsutures includes inserting a first end of a suture, optionally attachedto a needle, at an insertion point on the surface of a person's body.The first end of the suture may be pushed through soft tissue until thefirst end extends out of the soft tissue at an exit point. The first endof the suture may then be gripped and pulled to draw the first portionof the suture through the soft tissue so that a length of the firstportion of the suture remains in the soft tissue between the point ofinsertion and exit point of the first end. The soft tissue may then bemanually grouped and advanced along at least one portion of the sutureto provide the desired amount of lift.

Specific applications of cosmetic surgeries which may utilized thisphysical manipulation of a suture as described above include, forexample, facelifts, browlifts, thigh lifts, and breast lifts.

While the above description contains many specifics, these specificsshould not be construed as limitations on the scope of the disclosure,but merely as exemplifications of embodiments thereof. Those skilled inthe art will envision many other possibilities, including the use ofother wound closure devices, within the scope and spirit of thedisclosure as defined by the claims appended hereto.

What is claimed is:
 1. A surgical suture comprising: an elongated bodycomprising at least one filament having a proximal end and a distal end;the elongated body having barbs projecting from the elongated bodytowards at least one end of said suture thereby forming an angle betweenthe barbs and the elongated body; and an effective amount of a bioactiveagent disposed solely within the angle between the barbs and theelongated body.
 2. The surgical suture of claim 1, wherein the bioactiveagent is selected from the group consisting of biocidal agents,antimicrobial agents, medicaments, growth factors, anti-clotting agents,clotting agents, analgesics, anesthetics, anti-inflammatory agents,wound repair agents, chemotherapeutics, biologics, protein therapeutics,antibodies, DNA, RNA, peptides, polysaccharides, lectins, lipids,anti-angiogenic drugs, polymeric drugs, and combinations thereof.
 3. Thesurgical suture of claim 2, wherein the antimicrobial agent is selectedfrom the group consisting of antibiotics, antiseptics, disinfectants,and combinations thereof.
 4. The surgical suture of claim 3, wherein theantimicrobial agent is an antiseptic selected from the group consistingof hexachlorophene, chlorhexidine, cyclohexidine, iodine,povidone-iodine, p-chloro-m-xylenol, triclosan, nitrofurantoin,nitrofurazone, methenamine, glutaraldehyde, formaldehyde, alcohols, andcombinations thereof.
 5. The surgical suture of claim 2, wherein theantimicrobial agent is selected from the group consisting ofanthracycline, doxorubicin, mitoxantrone, a fluoropyrimidine,5-fluorouracil, a folic acid antagonist, methotrexate, podophylotoxin,etoposide, camptothecin, hydroxyurea, a platinum complex, cisplatin,doxycycline, metronidazole, trimethoprim-sulfamethoxazole, rifamycinslike rifampin, polyvinyl pyrrolidone, fourth generation penicillins andanalogues and derivatives thereof, a first generation cephalosporins andanalogues and derivatives thereof, a second generation cephalosporin andanalogues and derivatives thereof, a third generation cephalosporin andanalogues and derivatives thereof, a fourth generation cephalosporin andanalogues and derivatives thereof, a monobactam, a carbapenem, anaminoglycoside, a macrolide, a lincosamide, a streptogramin,erythromycin, azithromycin, clindamycin, syneroid, clarithromycin,kanamycin sulfate, tetracyclines, fusidic acid, trimethoprim,metronidazole; a quinolone, a DNA synthesis inhibitor, a sulfonamide,beta-lactam inhibitors, chloramphenicol, glycopeptides, mupirocin,polyenes, azoles, and combinations thereof.
 6. The surgical suture ofclaim 2, wherein the chemotherapeutics is selected from the groupconsisting of doxorubicin, paclitaxel, camptothecin, polyglutamate-PTX,N-(2-hydroxypropyl)methacrylamide copolymer, anthracycline, letrozole,anastrozole, epidermal growth factor receptor inhibitors, tyrosinekinase inhibitors, modulators of apoptosis, anthracycline antibioticssuch as daunorubicin and doxorubicin, alkylating agents such ascyclophosphamide and melphalan, antimetabolites such as methotrexate and5-fluorouracil, poly(ethylene glycol), poly(glutamic acid),polysaccharides, polymer-drug conjugates thereof, copolymers thereof andcombinations thereof.
 7. The surgical suture of claim 2, wherein theclotting agent is selected from the group consisting of human growthfactors, magainin, plasminogen activator, superoxide dismutase, tumornecrosis factor, colony stimulating factor, interferon, interleukin-2,lymphokines, fibrin, chitosin, silk, talc, polylysine, fibronectin,bleomycin and analogues and derivatives thereof, collagen, metallicberyllium and oxide thereof, copper, saracin, silica, crystallinesilicates, quartz dust, talcum powder, ethanol, extracellular matrix,fibrinogen, poly(ethylene terephthalate),poly(ethylene-co-vinylacetate), cyanoacrylate, cytokines, dexamethasone,isotretinoin, estradiols, diethylstibesterol, cyclosporine a, all-transretinoic acid and analogues and derivatives thereof, wool, cotton,polyurethane, polytetrafluoroethylene, poly(alkylcyanoacrylate),activin, angiopoietin, colony-stimulating factor, erythropoietin,endothelin-1, angiotensin II, bromocriptine, methylsergide, fibrosin,glycoproteins, proteoglycan, hyaluronan, secreted protein acidic andrich in cysteine, a thrombospondin, tenacin, a cell adhesion molecule,an inhibitor of matrix metalloproteinase, methotrexate, carbontetrachloride, thioacetamide, superoxide dismutase, tumor necrosisfactor, colony stimulating factor, platelet rich plasma, thrombin, andcombinations thereof.
 8. The surgical suture of claim 1, wherein thesuture is a monofilament suture.
 9. The surgical suture of claim 1,wherein the suture is a multifilament suture.
 10. The surgical suture ofclaim 1, wherein the at least one filament is made from a materialselected from the group consisting of degradable materials,non-degradable materials, and combinations thereof.
 11. The surgicalsuture of claim 1, wherein the at least one filament comprises adegradable material selected from the group consisting of trimethylenecarbonate, tetramethylene carbonate, caprolactone, valerolactone,dioxanone, glycolic acid, lactic acid, glycolide, polyanhydrides,polyesters, polyacrylates, polymethylmethacrylates, polyurethanes,polyorthoester, polyhydroxy alkanoates, polyhydroxy butyrate, lactide,polymer drugs, homopolymers thereof, copolymers thereof, andcombinations thereof.
 12. The surgical suture of claim 11, wherein thepolymer drugs is selected from the group consisting of steroidalanti-inflammatory agents, non-steroidal anti-inflammatory agents, andcombinations thereof.
 13. The surgical suture of claim 12, wherein thenon-steroidal anti-inflammatory agent is selected from the groupconsisting of aspirin, indomethacin, ibuprofen, phenylbutazone,diflusinal and combinations thereof.
 14. The surgical suture of claim12, wherein the steroidal anti-inflammatory agent is selected from thegroup consisting of glucocorticoids such as cortisone andhydrocortisone, betamethasone, dexamethasone, fluprednisolone,prednisone, methylprednisolone, prednisolone, triamcinolone,paramethasone, and combinations thereof.
 15. The surgical suture ofclaim 1, wherein the at least one filament comprises a non-degradablematerial selected from the group consisting of polyethylene,polypropylene, copolymers of polyethylene and polypropylene, blends ofpolyethylene and polypropylene, polyethylene terephthalate,polytetrafluoroethylene, polybutester, polytetramethylene ether glycol,1,4-butanediol, silk, collagen, ultrahigh molecular weight polyethyleneand combinations thereof.
 16. The surgical suture of claim 1, furthercomprising a coating on at least a portion of the suture.
 17. Thesurgical suture of claim 16, wherein the coating comprises a degradablepolymer.
 18. The surgical suture of claim 16, wherein the coating isselected from the group consisting of trimethylene carbonate,tetramethylene carbonate, caprolactone, valerolactone, dioxanone,glycolic acid, lactic acid, glycolide, polyanhydrides, polyesters,polyacrylates, polymethylmethacrylates, polyurethanes, polyorthoester,polyhydroxy alkanoates, polyhydroxy butyrate, lactide, polymer drugs,homopolymers thereof, copolymers thereof, and combinations thereof. 19.The surgical suture of claim 16, wherein the coating further comprisesat least one monomer selected from the group consisting of alkylenecarbonates, dioxanones, dioxepanones, degradable cyclic amides,degradable cyclic ether-esters derived from crown ethers, alphahydroxyacids, beta hydroxyacids, polyalkyl ethers, polyvinylpyrrolidone, hydroxyethylmethacrylate, phosphorylcholine, acrylic acid,methacrylic acid, vinyl monomers, vinyl alcohols, vinyl acetate, andcombinations thereof.
 20. The surgical suture of claim 16, wherein thecoating further comprises one or more fatty acid components selectedfrom the group consisting of fatty acids, fatty acid salts and salts offatty acid esters.
 21. The surgical suture of claim 1, wherein the anglebetween the barbs and the suture body is less than 90 degrees.
 22. Amethod comprising closing a wound with a suture of claim
 1. 23. Themethod of claim 22, wherein the suture is affixed to a needle.
 24. Themethod of claim 22, wherein the suture is advanced through tissue withina tubular insertion device.
 25. The surgical suture of claim 1, whereinthe barbs are integrally formed with the elongated body.